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One-way membrane trafficking of SOS in receptor-triggered Ras activation

SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane-recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2:SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide...

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Autores principales: Christensen, Sune M., Tu, Hsiung-Lin, Jun, Jesse E., Alvarez, Steven, Triplet, Meredith G., Iwig, Jeffrey S., Yadav, Kamlesh K., Bar-Sagi, Dafna, Roose, Jeroen P., Groves, Jay T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016256/
https://www.ncbi.nlm.nih.gov/pubmed/27501536
http://dx.doi.org/10.1038/nsmb.3275
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author Christensen, Sune M.
Tu, Hsiung-Lin
Jun, Jesse E.
Alvarez, Steven
Triplet, Meredith G.
Iwig, Jeffrey S.
Yadav, Kamlesh K.
Bar-Sagi, Dafna
Roose, Jeroen P.
Groves, Jay T.
author_facet Christensen, Sune M.
Tu, Hsiung-Lin
Jun, Jesse E.
Alvarez, Steven
Triplet, Meredith G.
Iwig, Jeffrey S.
Yadav, Kamlesh K.
Bar-Sagi, Dafna
Roose, Jeroen P.
Groves, Jay T.
author_sort Christensen, Sune M.
collection PubMed
description SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane-recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2:SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide linkage to the membrane. In reconstituted membrane experiments, these Grb2-independent interactions are sufficient to retain SOS on the membrane for many minutes, during which a single SOS molecule can processively activate thousands of Ras molecules. These observations raise questions concerning how receptors maintain control of SOS in cells and how membrane-recruited SOS is ultimately released. We addressed these questions in quantitative reconstituted SOS-deficient chicken B cell signaling systems combined with single molecule measurements in supported membranes. These studies reveal an essentially one-way trafficking process in which membrane-recruited SOS remains trapped on the membrane and continuously activates Ras until it is actively removed via endocytosis.
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spelling pubmed-50162562017-02-08 One-way membrane trafficking of SOS in receptor-triggered Ras activation Christensen, Sune M. Tu, Hsiung-Lin Jun, Jesse E. Alvarez, Steven Triplet, Meredith G. Iwig, Jeffrey S. Yadav, Kamlesh K. Bar-Sagi, Dafna Roose, Jeroen P. Groves, Jay T. Nat Struct Mol Biol Article SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane-recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2:SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide linkage to the membrane. In reconstituted membrane experiments, these Grb2-independent interactions are sufficient to retain SOS on the membrane for many minutes, during which a single SOS molecule can processively activate thousands of Ras molecules. These observations raise questions concerning how receptors maintain control of SOS in cells and how membrane-recruited SOS is ultimately released. We addressed these questions in quantitative reconstituted SOS-deficient chicken B cell signaling systems combined with single molecule measurements in supported membranes. These studies reveal an essentially one-way trafficking process in which membrane-recruited SOS remains trapped on the membrane and continuously activates Ras until it is actively removed via endocytosis. 2016-08-08 2016-09 /pmc/articles/PMC5016256/ /pubmed/27501536 http://dx.doi.org/10.1038/nsmb.3275 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Christensen, Sune M.
Tu, Hsiung-Lin
Jun, Jesse E.
Alvarez, Steven
Triplet, Meredith G.
Iwig, Jeffrey S.
Yadav, Kamlesh K.
Bar-Sagi, Dafna
Roose, Jeroen P.
Groves, Jay T.
One-way membrane trafficking of SOS in receptor-triggered Ras activation
title One-way membrane trafficking of SOS in receptor-triggered Ras activation
title_full One-way membrane trafficking of SOS in receptor-triggered Ras activation
title_fullStr One-way membrane trafficking of SOS in receptor-triggered Ras activation
title_full_unstemmed One-way membrane trafficking of SOS in receptor-triggered Ras activation
title_short One-way membrane trafficking of SOS in receptor-triggered Ras activation
title_sort one-way membrane trafficking of sos in receptor-triggered ras activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016256/
https://www.ncbi.nlm.nih.gov/pubmed/27501536
http://dx.doi.org/10.1038/nsmb.3275
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